Feature Finding Title
Feature Finding Figure

Levels of mRNA for the α1 subunit of the GABAA receptor, which is present in 60% of cortical GABAA receptors, have been reported to be lower in layer 3 of the prefrontal cortex in subjects with schizophrenia. This subunit is expressed in both pyramidal cells and interneurons, and thus lower α1 subunit levels in each cell population would have opposite effects on net cortical excitation. We used dual-label in situ hybridization to quantify GABAA α1 subunit mRNA expression in calcium/calmodulin-dependent kinase II α (CaMKIIα)-containing pyramidal cells (circles in panel A) and glutamic acid decarboxylase 65 kDa (GAD65)-containing interneurons (circles in panel B) in layer 3 of the PFC from matched schizophrenia and healthy comparison subjects. In subjects with schizophrenia, mean GABAA α1 subunit mRNA expression was significantly 40% lower in pyramidal cells (panel C), but was not altered in interneurons (panel D). Lower α1 subunit mRNA expression in pyramidal cells was not attributable to potential confounding factors, and thus appeared to reflect the disease process of schizophrenia. These results suggest that pyramidal cell inhibition is reduced in schizophrenia, whereas inhibition of GABA neurons is maintained. The cell type specificity of these findings may reflect a compensatory response to enhance layer 3 pyramidal cell activity in the face of diminished excitatory drive associated with the lower dendritic spine density on these neurons.

Glausier JR and Lewis DA: Selective Pyramidal Cell Reduction of GABAA Receptor a1 Subunit Expression in Schizophrenia. Neuropsychopharmacology, 36:2103-2110, 2011.

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David A. Lewis, M.D. | Department of Psychiatry | University of Pittsburgh
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